Spontaneous photo‐relaxation of urethral smooth muscle from sheep, pig and rat and its relationship with nitrergic neurotransmission

Triguero, Domingo; Costa, Gonzalo; Labadía, A.; Jiménez, Eugenio; Garcia-Pascual, Angeles

doi:10.1111/j.1469-7793.2000.00443.x

Cited by 13 publications

(14 citation statements)

References 42 publications

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“…Cellular NO stores have been previously shown to be photosensitive S-nitrosothiols, compounds that release NO under light stimulation and become depleted after a few minutes (8,26,36). This effect is depicted in Fig.…”

Section: Discussionmentioning

confidence: 82%

“…In the present study, we determined the effect of renal tissue thiol depletion caused by BSO, a glutathione depletor that induces a rapid decrease in tissue GSH due to specific inhibition of ␥-glutamylcysteine synthetase (11), and renal exposure to a cold light source, known to release NO by decomposing nitrosothiols (8,26,36). We observed a 74.5% decrease in the renal concentration of sulfhydryl groups 150 min after BSO injection, which is similar to values previously reported (29), and an 80.4% decrease after 90 min of cold light exposure.…”

Section: Discussionmentioning

confidence: 99%

“…To demonstrate that the effects of BSO are specific and not due to a side effect of this compound, the actions of N-acetyl-L-cysteine (NAC), a sulfhydryl group donor, in preventing the effects of BSO were studied. Finally, because light releases NO from nitrosothiols (8,26,36), it was determined whether the depletion of renal …”

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confidence: 99%

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Renal ischemia induces an increase in nitric oxide levels from tissue stores

Salom

Arregui²,

Carbonell³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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Tissue nitric oxide (NO) levels increase dramatically during ischemia, an effect that has been shown to be partially independent from NO synthases. Because NO is stored in tissues as S-nitrosothiols and because these compounds could release NO during ischemia, we evaluated the effects of buthionine sulfoximine (BSO; an intracellular glutathione depletor), light stimulation (which releases NO, decomposing S-nitrosothiols), and N-acetyl-L-cysteine (a sulfhydryl group donor that repletes S-nitrosothiols stores) on the changes in outer medullary NO concentration produced during 45 min of renal artery occlusion in anesthetized rats. Renal ischemia increased renal tissue NO concentration (ϩ223%), and this effect was maintained along 45 min of renal arterial blockade. After reperfusion, NO concentration fell below preischemic values and remained stable for the remainder of the experiment. Pretreatment with 10 mg/kg nitro-L-arginine methyl ester (L-NAME) decreased significantly basal NO concentration before ischemia, but it did not modify the rise in NO levels observed during ischemia. In rats pretreated with 4 mmol/kg BSO and L-NAME, ischemia was followed by a transient increase in renal NO concentration that fell to preischemic values 20 min before reperfusion. A similar response was observed when the kidney was illuminated 40 min before the ischemia. The coadministration of 10 mg/kg iv N-acetyl-L-cysteine with BSO ϩ L-NAME restored the increase in NO levels observed during renal ischemia and prevented the depletion of renal thiol groups. These results demonstrate that the increase in renal NO concentration observed during ischemia originates from thiol-dependent tissue stores. voltammetry; nitrosothiols; N-acetyl-L-cysteine; buthionine sulfoximine; photosensitive nitric oxide release IT HAS BEEN REPORTED THAT arterial ischemia produces an abrupt and significant increase in tissue nitric oxide (NO) concentration, which can last as long as ischemia is maintained and returns to preischemic levels during reperfusion. This phenomenon has been observed in kidney (27), liver (16), heart (40), gastric tissue (15), and brain (39); although its physiological relevance is unclear, it may generate the high levels of peroxynitrite anion formed during reperfusion when a burst of superoxide anion reacts with the high levels of NO accumulated during ischemia (21), thus contributing to reperfusion damage. The mechanism responsible for these increased NO levels during renal ischemia is unknown, although it seems to be partially insensitive to NO synthesis inhibition, at least in liver and kidney (16,27). This is not surprising because NO synthase (NOS) requires molecular oxygen. Therefore, during ischemia, NO must be released from other sources, such as tissue NO stores (22,26,31).In the presence of oxygen, NO is synthesized from Larginine through the action of NOS, and this gaseous hormone acts in the kidney by stimulating guanylyl cyclase and by inhibiting cytochrome P-450 (18). However, as soon as it is synthesized, NO avidly react...

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Renal ischemia induces an increase in nitric oxide levels from tissue stores

Salom

Arregui²,

Carbonell³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Electrical field stimulation (EFS) of the sheep urethra induces non-adrenergic non-cholinergic (NANC) relaxation (García-Pascual et al 1991) that is mediated by increases in cGMP levels (García-Pascual and Triguero 1994) and blocked by nitric oxide (NO) synthesis inhibitors (García-Pascual et al 1991;Triguero et al 2000). In addition, the presence of constitutive NO synthase (NOS) activity in nerve fibres in the smooth muscle layer of the urethra has been shown (Triguero et al 1993;García-Pascual et al 1996).…”

Section: Introductionmentioning

confidence: 98%

Nitrergic relaxation in urethral smooth muscle: involvement of potassium channels and alternative redox forms of NO

Costa

Labadía²,

Triguero³

et al. 2001

Naunyn-Schmied Arch Pharmacol

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We examined the contribution of K+ channels to the relaxation responses induced by different redox forms of nitric oxide (NO., NO- and NO+) in comparison with those evoked by electrical field stimulation (EFS) of nitrergic nerves in the sheep urethra. K+ channel blockers with different selectivity profile were used. Sodium nitroprusside (SNP) and different S-nitrosothiols were used as NO+ donors, Angeli's salt as an NO- donor and nitroglycerin (GTN) was chosen as a representative compound known to require metabolic activation in the target tissue. Pure NO gas was used to prepare NO. solutions. Relaxation evoked by EFS of nitrergic nerves or by exogenous NO was not inhibited by any of the K+ channel blockers, but was enhanced by 4-aminopyridine [inhibitor of voltage-dependent K+ (KV) channels]. This suggests that, whereas K+ channel activation and hyperpolarization of the postsynaptic membrane do not contribute to relaxation, prejunctional modulation of the nitrergic neurotransmission by Kv channels may be relevant. Relaxation induced by NO+ or NO- donors was not affected by K+ channel blockade with the following exceptions: glybenclamide, a blocker of ATP-sensitive K+ channels (KATP), enhanced responses to SNP and Angeli's salt, 4-aminopyridine inhibited relaxation evoked by Angeli's salt and GTN, and charybdotoxin, a blocker of large-conductance, Ca2+-activated K+ channels (BKCa) inhibited those induced by the S-nitrosothiol S-nitrosoglutathione. These results do not suggest the existence of a general mechanism of action on K+ channels for compounds releasing either NO+ or NO- in the sheep urethra. None of the K+ channel blockers affected relaxation induced by the membrane-permeable analogue of cGMP, 8-bromo-cGMP. However, the fact that the addition of the phosphodiesterase inhibitor zaprinast (0.1 mM) enhanced the relaxation to Angeli's salt, while preventing the inhibition induced by 4-aminopyridine, suggests that involvement of guanylate cyclase activation in the action of NO donors on K+ channels can not be excluded. Accordingly, the guanylate cyclase inhibitors 1H-[1,2,4]-oxadiazole-[4,3-a]-quinoxalin-1-one (ODQ, 10 microM) and 4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one (NS 2028, 10 microM) almost abolished relaxations to EFS and Angeli's salt. In contrast, ODQ only moderately inhibited relaxations to NO.. In addition, the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl imidazoline-1-oxyl 3-oxide (carboxy-PTIO) effectively inhibited responses to NO. whilst not affecting those to EFS or NO-, suggesting a close similarity between the nitrergic transmitter and nitroxyl ion. We conclude that nitrergic relaxation induced either by the endogenous transmitter or by exogenous NO donors in the ovine urethra is not mediated by postsynaptic alterations in the K+ conductance; only a prejunctional modulation through Kv channels seems to be significant. In addition, the production and/or release of alternative redox forms of NO, such as NO-, may be involved in neurotransmission processes in the urethra.

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“…Although initially thought to be restricted to blood vessels, a similar PR has also been described in some non-vascular smooth muscle structures such as the dog and mouse gastric fundus [9,10] or the urethra from different species [11]. All these structures are supplied with a dense network of nitrergic fibers, which mediate relaxation elicited by electrical field stimulation (EFS).…”

Section: Introductionmentioning

confidence: 97%

Localization and thiol dependancy of endogenous nitro compounds-mediating urethral photo-relaxation

Triguero

González-Herreros

Costa

et al. 2007

Pflugers Arch - Eur J Physiol

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Using a nitric oxide (NO)-specific fluorescent probe, we have examined the location of NO generation in the urethra from sheep and rat when induced by either electrical field- or light-stimulation (EFS and LS, respectively). In addition, we studied the effect of specific glutathione (GSH) modifiers, acting upon different cellular GSH pools, on NO release and on urethral relaxation. Both EFS and LS led to fluorescence emission from a fiber network associated with neuronal NO synthase (nNOS) immunoreactive nerves. Both the relaxation and the fluorescence elicited by EFS were blocked by specific nNOS inhibitors, but these parameters were not significantly modified by endogenous GSH depletion. In contrast, the opposite was found for LS-induced responses. Moreover, when the mitochondrial pool was effectively reduced by incubation with ethacrynic acid, the responses to LS were further reduced until they disappeared after intensive LS. Our results confirm that while NO is released by nNOS activation, the photolytic breakdown of an endogenous nitro-compound, probably S-nitroso-glutathione, in nitrergic nerves (and in the vascular endothelium) is the only factor responsible for photo-relaxation. The possible role of this mechanism in NO inactivation and as a protective mechanism in NO-generating structures is further discussed.

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Spontaneous photo‐relaxation of urethral smooth muscle from sheep, pig and rat and its relationship with nitrergic neurotransmission

Cited by 13 publications

References 42 publications

Renal ischemia induces an increase in nitric oxide levels from tissue stores

Renal ischemia induces an increase in nitric oxide levels from tissue stores

Nitrergic relaxation in urethral smooth muscle: involvement of potassium channels and alternative redox forms of NO

Localization and thiol dependancy of endogenous nitro compounds-mediating urethral photo-relaxation

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